Without limiting the scope of the invention, its background is described in connection with the existing understanding of heart failure. The myocardium, when stressed from a variety of causes including myocardial infarction (MI), coronary artery disease, hypertension, cardiomyopathy, myocarditis, valvular regurgitation, severe lung disease, and severe anemia of chronic disease, may develop increasing dysfunction and go on to apoptosis of cardiocytes and a detrimental remodeling of the myocardium. This progression ultimately results in the clinical entity of chronic heart failure (CHF), also known as chronic cardiac failure (CCF) or chronic congestive heart failure. The present invention is focused on an important distinction between the inciting cardiac lesion, whether myocardial infarction, valve disease etc., and the remote, often normal, myocardium. It is this remote myocardium that suffers compensatory stress and which descends into failure. Also of importance to the present invention is a recognition that the dysfunction which may affect the normal or remote myocardium is often progressive in nature. Although this progression has been well documented and recognized, what controls it is unknown
According to national surveys, an estimated 4.8 million Americans have congestive heart failure, divided equally between men and women. Of these, almost 1.4 million are under 60 years of age. Prevalence of CHF is increasing substantially with an estimated 400,000 new cases each year according to National Heart, Lung, and Blood Institute (NHLBI) statistics. As CHF is the end stage of cardiac disease, half of the patients diagnosed with CHF will be dead within 5 years. Increasing prevalence, hospitalizations, and deaths have made CHF a major chronic problem in the United States and the most common cause of hospitalization.
CHF treatments are currently limited to alleviating symptoms of existing heart failure including through significant life style changes, medications such as diuretics and ACE inhibitors which can have significant side effects, and surgery. All current treatments for heart disease which do not treat the inciting lesions themselves (i.e., coronary artery stents, valve replacements, etc.) are secondary in nature. Some medications, for example, will produce dilation of the vessels in the body and, therefore, reduce the resistance to blood flow which the heart must overcome. This does not treat the cardiomyocytes directly but it does reduce the work the heart must do, providing secondary benefit. No measures currently exist, however, that directly prevent or even ameliorate root causes of the progression to CHF.
From the foregoing it is apparent the there is a need in the art for compositions and methods for preventing or significantly slowing the progressive damage to the myocardium which results in CHF. The invention described provides a novel method and compositions which significantly reduces the progression to CHF in individuals at risk for development.